RESUMO
Reactive oxygen species (ROS) are central to inter- and intracellular signaling. Their localized and transient effects are due to their short half-life, especially when generated in controlled amounts. Upon T cell receptor (TCR) activation, regulated ROS signaling is primarily initiated by complexes I and III of the electron transport chain (ETC). Subsequent ROS production triggers the activation of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2), prolonging the oxidative signal. This signal then engages kinase signaling cascades such as the mitogen-activated protein kinase (MAPK) pathway and increases the activity of REDOX-sensitive transcription factors such as nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). To limit ROS overproduction and prevent oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant proteins such as superoxide dismutases (SODs) finely regulate signal intensity and are capable of terminating the oxidative signal when needed. Thus, oxidative signals, such as T cell activation, are well-controlled and critical for cellular communication.
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Espécies Reativas de Oxigênio , Transdução de Sinais , Linfócitos T , Espécies Reativas de Oxigênio/metabolismo , Humanos , Linfócitos T/metabolismo , Linfócitos T/imunologia , Animais , Ativação Linfocitária , Estresse Oxidativo , Oxirredução , Receptores de Antígenos de Linfócitos T/metabolismo , Fator 2 Relacionado a NF-E2/metabolismoRESUMO
BACKGROUND: Partial splenic embolization (PSE) is a non-surgical procedure which was initially used to treat hypersplenism. Furthermore, partial splenic embolization can be used for the treatment of different conditions, including gastroesophageal variceal hemorrhage. Here, we evaluated the safety and efficacy of emergency and non-emergency PSE in patients with gastroesophageal variceal hemorrhage and recurrent portal hypertensive gastropathy bleeding due to cirrhotic (CPH) and non-cirrhotic portal hypertension (NCPH). METHODS: From December 2014 to July 2022, twenty-five patients with persistent esophageal variceal hemorrhage (EVH) and gastric variceal hemorrhage (GVH), recurrent EVH and GVH, controlled EVH with a high risk of recurrent bleeding, controlled GVH with a high risk of rebleeding, and portal hypertensive gastropathy due to CPH and NCPH underwent emergency and non-emergency PSE. PSE for treatment of persistent EVH and GVH was defined as emergency PSE. In all patients pharmacological and endoscopic treatment alone had not been sufficient to control variceal bleeding, and the placement of a transjugular intrahepatic portosystemic shunt (TIPS) was contraindicated, not reasonable due to portal hemodynamics, or TIPS failure with recurrent esophageal bleeding had occurred. The patients were followed-up for six months. RESULTS: All twenty-five patients, 12 with CPH and 13 with NCPH were successfully treated with PSE. In 13 out of 25 (52%) patients, PSE was performed under emergency conditions due to persistent EVH and GVH, clearly stopping the bleeding. Follow-up gastroscopy showed a significant regression of esophageal and gastric varices, classified as grade II or lower according to Paquet's classification after PSE in comparison to grade III to IV before PSE. During the follow-up period, no variceal re-bleeding occurred, neither in patients who were treated under emergency conditions nor in patients with non-emergency PSE. Furthermore, platelet count increased starting from day one after PSE, and after one week, thrombocyte levels had improved significantly. After six months, there was a sustained increase in the thrombocyte count at significantly higher levels. Fever, abdominal pain, and an increase in leucocyte count were transient side effects of the procedure. Severe complications were not observed. CONCLUSION: This is the first study analyzing the efficacy of emergency and non-emergency PSE for the treatment of gastroesophageal hemorrhage and recurrent portal hypertensive gastropathy bleeding in patients with CPH and NCPH. We show that PSE is a successful rescue therapy for patients in whom pharmacological and endoscopic treatment options fail and the placement of a TIPS is contraindicated. In critically ill CPH and NCPH patients with fulminant gastroesophageal variceal bleeding, PSE showed good results and is therefore an effective tool for the rescue and emergency management of gastroesophageal hemorrhage.
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Embolização Terapêutica , Varizes Esofágicas e Gástricas , Hipertensão Portal , Humanos , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Tratamento de Emergência , Hipertensão Portal/complicaçõesRESUMO
BACKGROUND: Acute severe pancreatitis is associated with high morbidity and mortality. Hypertriglyceridemia is the third most common cause of acute pancreatitis and higher triglyceride levels increase the risk for severe acute pancreatitis. Plasma exchange is an effective treatment method to lower triglycerides. Our study aimed to investigate the efficiency of plasma exchange as a treatment option for acute hypertriglyceridemia-induced pancreatitis (HTGP), the impact on mortality assessed by the SOFA, SAPS II, BISAP Score, Ranson's, and Glasgow-Imrie Criteria, as well as the overall length of stay in hospital and ICU. METHODS: In this retrospective single-center cohort study, triglycerides before and after plasma exchange were compared. SOFA and SAPS II were taken on ICU admission and at discharge. To further characterize the patient cohort, BISAP Score (on admission), Ranson's Criteria (on admission and after 48 h), and the Glasgow-Imrie Criteria (48 h after admission) were calculated. RESULTS: The study included 11 patients (91% male; median age 45 years). Triglycerides were reduced from 4,266 ± 3,560.6 to 842 ± 575.9 mg/dL during plasmapheresis (p < 0.001). The median ICU length of stay was 3 ± 4.2 days. In-hospital mortality was 0%. The SOFA score was significantly reduced from 4 ± 3.4 points on admission to 2 ± 2.1 points at discharge (p = 0.017). Triglycerides and cholesterol decreased from 3,126 ± 3,665 to 531 ± 273 mg/dL (p = 0.003) and from 438 ± 137.9 to 222 ± 59.5 mg/dL (p = 0.028), respectively. The BISAP Score on admission was 3 ± 0.5 points, Ranson's Criteria were 3 ± 1.5 points (48 h after admission, cumulative), and Glasgow-Imrie Criteria 3 ± 1.3 points (48 h after admission). CONCLUSION: Plasmapheresis is an efficient and safe treatment method for ICU patients with acute HTGP and significantly reduces triglycerides. Furthermore, plasmapheresis significantly improves the clinical outcomes of patients with HTGP.
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Hipertrigliceridemia , Pancreatite , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Pancreatite/etiologia , Pancreatite/terapia , Troca Plasmática/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Doença Aguda , Plasmaferese/efeitos adversos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/terapia , Triglicerídeos , Unidades de Terapia IntensivaRESUMO
T cell depletion and functional impairment are characteristics of sepsis. CD137 is a costimulatory receptor on activated T cells, while soluble CD137 (sCD137) inhibits CD137 signaling. This study found elevated sCD137 levels in the plasma of patients with systemic inflammatory response syndrome (SIRS), sepsis, or septic shock compared to healthy controls. The sCD137 levels negatively correlated with the C-reactive protein and positively with procalcitonin and interleukin-6. There was no difference in sCD137 levels based on ventilation, dialysis, or vasopressor treatment. Patients with SARS-CoV-2, Gram-positive, or Gram-negative bacterial infections had similar sCD137 levels as noninfected individuals. Notably, higher plasma sCD137 levels were observed in non-survivors compared to survivors in both the SIRS/sepsis group and the SARS-CoV-2 subgroup. In conclusion, plasma sCD137 levels are associated with severe illness and survival in critically ill patients.
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Estado Terminal , Sepse , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral , Humanos , Biomarcadores , Prognóstico , Receptores do Fator de Necrose Tumoral , Diálise Renal , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/químicaRESUMO
Background and Objectives: Alveolar echinococcosis (AE) is a highly variable disease able to present as structurally diverse cysts in different organs based on the host's immunological state as well as the time between diagnosis and the primary infection. Bacterial superinfections, especially with anaerobic pathogens from the Clostridiaceae genus, can further alter the radiological findings due to pneumobilia, newly formed abscess formations, and inflammatory changes. Materials and Methods: We present a case of a 71-year-old Caucasian male admitted to our intensive care unit with septic shock, pneumobilia, and a complex cyst of the liver with calcification, as shown by an initial CT. Because of the septic shock, the patient was started on broad-band antibiotics. Clostridiaceae infection was considered an important differential diagnosis due to the presence of pneumobilia observed in the initial CT, without a history of previous endoscopy. Furthermore, serology for echinococcus was positive, and blood cultures showed growth of C. perfringens. Therefore, the patient was additionally treated with albendazole. After recovery, further staging was conducted, showing complete remission of the cyst and a left-over lesion classified as Alveolar Echinococcosis Ulm Classification (AEUC) V. In summary, the patient had a pre-existing, controlled AE infection that became superinfected with C. perfringens, likely attributable to the anaerobic necrotic tissue, leading to septicemia. Results: The anaerobic tissue within the AE cyst provided an ideal medium for C. perfringens to replicate, leading to cyst infection, which subsequently caused septic shock and pneumobilia. The initial findings from CT and MRI were confounded by the superinfection, demonstrating the diagnostic challenges of AE, especially when presenting with complications. Conclusions: Diagnosing AE remains a demanding task, even with the excellent tools available through serology, coupled with CT, FDG-PET-CT, and MRI. Notably, older superinfected cysts can pose difficulties when integrated into the appropriate diagnostic context. Prompt diagnosis is critical for the accurate treatment of echinococcosis and its complications, such as bacterial superinfections. From a clinical perspective, septicemia from Clostridiaceae and infections with C. perfringens-pathogens capable of inducing pneumobilia-should be regarded as significant differential diagnoses for pneumobilia in the absence of a recent history of endoscopy.
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Infecções Bacterianas , Cistos , Equinococose , Echinococcus , Sepse , Choque Séptico , Superinfecção , Animais , Humanos , Masculino , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Equinococose/diagnóstico , Sepse/complicações , Sepse/diagnósticoRESUMO
BACKGROUND: From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties. METHODS: We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens. RESULTS: The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%. CONCLUSIONS: Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.
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COVID-19/diagnóstico , SARS-CoV-2 , Soroconversão , Carga Viral , Adulto , Anticorpos Antivirais , Antígenos Virais , COVID-19/imunologia , Feminino , Humanos , Masculino , Saúde Pública , RNA Viral , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Índice de Gravidade de DoençaRESUMO
Background and Objectives: With more and more cases emerging outside central and west African countries, where the disease is endemic, the World Health Organization (WHO) has recently declared human monkeypox a Public Health Emergency of International Concern. Typical symptoms of the disease include fever, myalgia, and lymphadenopathy followed by a rash, but other symptoms may occur. Immunocompromised patients, including patients with uncontrolled Human Immunodeficiency Virus (HIV) infection, may be at risk for more severe courses. Case presentation: We present the case of a 30-year-old male patient of Brazilian descent with monkeypox. Initial symptoms were fever and general discomfort, with painful pharyngitis and tonsillitis and finally a papular rash of the anogenital area as the disease progressed. The presumed date of infection was a sexual contact with an unknown male eight days before the first symptoms occurred. The patient had a known and controlled HIV infection. The main reason for the initial presentation at the hospital was painful pharyngitis and tonsillitis, limiting food intake. Monkeypox infection was confirmed via PCR testing from a swab sample of cutaneous lesions. Adequate systemic and local analgesia enabled oral food uptake again. Antiviral therapy with Tecovirimat was not administered due to the stable immune status of the patient and the mild clinical symptoms. To cover a possible bacterial superinfection or Syphilis infection of the tonsil, antibiotic therapy with Ceftriaxone was added. Several days after presentation, the inflammation of the pharynx resolved and was followed by non-painful mucosal peeling. The patient was followed up with telephone calls and reported a complete recovery. The skin lesions were completely dried out 18 days after the first symptoms. Conclusions: Painful pharyngitis and tonsillitis can be rare early symptoms of monkeypox, which is highly relevant in everyday clinical practice. Particularly in patients with risk factors for monkeypox infection, further clinical and microbiologic testing for monkeypox should be performed if there is a clinical presentation with pharyngitis and tonsillitis.
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Exantema , Infecções por HIV , Mpox , Faringite , Tonsilite , Humanos , Masculino , Adulto , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Mpox/complicações , Ceftriaxona , Tonsilite/complicações , Tonsilite/tratamento farmacológico , Tonsilite/diagnóstico , Faringite/complicações , Faringite/tratamento farmacológico , Febre/complicações , Antivirais , Antibacterianos , Exantema/complicaçõesRESUMO
OBJECTIVE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels. METHODS: In our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated. RESULTS: The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%; N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection; N = 53) in serum. CONCLUSIONS: With the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.
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Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , COVID-19/diagnóstico , Ensaio de Imunoadsorção Enzimática/normas , Testes de Neutralização/normas , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Neutralizantes/sangue , Antígenos Virais/química , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Estudos Transversais , Humanos , Soros Imunes/química , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Domínios Proteicos , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/químicaRESUMO
BACKGROUND: In Germany, following the principle "sickest first", patients awaiting liver transplantation (LTPL) are often transplanted with high MELD score and run the risk that they can no longer be transplanted, getting "too sick for transplant". METHODS: In a retrospective single-center study, we analyzed the mortality of adult patients on the waiting list for LTPL during the years 2014 to 2017. To stratify risk factors, we compared characteristics of deceased and transplanted patients. RESULTS: The main reasons for mortality were sepsis (42.9â%), malignancy (24.3â%) and bleeding (10.0â%). Risk factors for mortality (OR, univariate logistic regression, pâ<â0.05) were acute on chronic liver failure (ACLF), loss of E-MELD, sepsis, pneumonia, proof of pathogens, candidemia, stay at ICU, multiple organ failure and mechanical ventilation. Multivariate analysis revealed pneumonia (pâ<â0.001) and high MELD (pâ=â0.031) as risk factors. Transplantation was more likely in patients with E-MELD. We suggest a Waiting List Mortality Index for Transplantation (WMIT), by dividing deceased patients to transplanted patients to assess mortality. Average WMIT in our cohort was 0.65. CONCLUSIONS: Mortality on the waiting list is mainly determined by pneumonia and infections in high-MELD patients. Therefore, patients with ACLF after infections should be prioritized for LTPL. A WMIT might suitably represent waiting list mortality.
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Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Transplante de Fígado/estatística & dados numéricos , Listas de Espera/mortalidade , Doença Hepática Terminal/complicações , Alemanha/epidemiologia , Humanos , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Obtenção de Tecidos e Órgãos/métodos , Resultado do TratamentoRESUMO
Plant growth and development of new organs depend on the continuous activity of the meristems. In the shoot, patterns of organ initiation are determined by PINFORMED (PIN)-dependent auxin distribution, while the undifferentiated state of meristem cells requires activity of KNOTTED LIKE HOMEOBOX (KNOX) transcription factors. Cell proliferation and differentiation of the root meristem are regulated by the largely antagonistic functions of auxin and cytokinins. It has previously been shown that the transcription factor JAGGED LATERAL ORGANS (JLO), a member of the LATERAL ORGAN BOUNDARY DOMAIN (LBD) family, coordinates KNOX and PIN expression in the shoot and promotes root meristem growth. Here we show that JLO is required for the establishment of the root stem cell niche, where it interacts with the auxin/PLETHORA pathway. Auxin signaling involves the AUX/IAA co-repressor proteins, ARF transcription factors and F-box receptors of the TIR1/AFB1-5 family. Because jlo mutants fail to degrade the AUX/IAA protein BODENLOS, root meristem development is inhibited. We also demonstrate that the expression levels of two auxin receptors, TIR1 and AFB1, are controlled by JLO dosage, and that the shoot and root defects of jlo mutants are alleviated in jlo plants expressing TIR1 and AFB1 from a transgene. The finding that the auxin sensitivity of a plant can be differentially regulated through control of auxin receptor expression can explain how different developmental processes can be integrated by the activity of a key transcription factor.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Ácidos Indolacéticos/metabolismo , Proteínas Repressoras/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Meristema/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Proteínas Repressoras/fisiologia , Transdução de SinaisRESUMO
In adult mammals, leukocyte recruitment follows a well-defined cascade of adhesion events enabling leukocytes to leave the circulatory system and transmigrate into tissue. Currently, it is unclear whether leukocyte recruitment proceeds in a similar fashion during fetal development. Considering the fact that the incidence of neonatal sepsis increases dramatically with decreasing gestational age in humans, we hypothesized that leukocyte recruitment may be acquired only late during fetal ontogeny. To test this, we developed a fetal intravital microscopy model in pregnant mice and, using LysEGFP (neutrophil reporter) mice, investigated leukocyte recruitment during fetal development. We show that fetal blood neutrophils acquire the ability to roll and adhere on inflamed yolk sac vessels during late fetal development, whereas at earlier embryonic stages (before day E15), rolling and adhesion were essentially absent. Accordingly, flow chamber experiments showed that fetal EGFP(+) blood cells underwent efficient adhesion only when they were harvested on or after E15. Fluorescence-activated cell sorter analysis on EGFP(+) fetal blood cells revealed that surface expression of CXCR2 and less pronounced P-selectin glycoprotein ligand-1 (PSGL-1) begin to increase only late in fetal life. Taken together, our findings demonstrate that inflammation-induced leukocyte recruitment is ontogenetically regulated and enables efficient neutrophil trafficking only during late fetal life.
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Movimento Celular/imunologia , Sistema Imunitário/embriologia , Leucócitos/citologia , Microvasos/embriologia , Saco Vitelino/embriologia , Animais , Adesão Celular/imunologia , Eritroblastos/citologia , Feminino , Sangue Fetal/citologia , Proteínas de Fluorescência Verde/metabolismo , Sistema Imunitário/citologia , Migração e Rolagem de Leucócitos/imunologia , Leucócitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Microvasos/citologia , Microvasos/imunologia , Neutrófilos/citologia , Neutrófilos/metabolismo , Selectina-P/metabolismo , Gravidez , Receptores de Interleucina-8B/metabolismo , Saco Vitelino/irrigação sanguínea , Saco Vitelino/citologiaRESUMO
Multicellular organisms depend on cell production, cell fate specification, and correct patterning to shape their adult body. In plants, auxin plays a prominent role in the timely coordination of these different cellular processes. A well-studied example is lateral root initiation, in which auxin triggers founder cell specification and cell cycle activation of xylem pole-positioned pericycle cells. Here, we report that the E2Fa transcription factor of Arabidopsis thaliana is an essential component that regulates the asymmetric cell division marking lateral root initiation. Moreover, we demonstrate that E2Fa expression is regulated by the LATERAL ORGAN BOUNDARY DOMAIN18/LATERAL ORGAN BOUNDARY DOMAIN33 (LBD18/LBD33) dimer that is, in turn, regulated by the auxin signaling pathway. LBD18/LBD33 mediates lateral root organogenesis through E2Fa transcriptional activation, whereas E2Fa expression under control of the LBD18 promoter eliminates the need for LBD18. Besides lateral root initiation, vascular patterning is disrupted in E2Fa knockout plants, similarly as it is affected in auxin signaling and lbd mutants, indicating that the transcriptional induction of E2Fa through LBDs represents a general mechanism for auxin-dependent cell cycle activation. Our data illustrate how a conserved mechanism driving cell cycle entry has been adapted evolutionarily to connect auxin signaling with control of processes determining plant architecture.
Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Ciclo Celular/fisiologia , Fatores de Transcrição E2F/genética , Ácidos Indolacéticos/metabolismo , Raízes de Plantas/fisiologia , Arabidopsis/citologia , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição E2F/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Técnicas de Inativação de Genes , Mutagênese Insercional , Raízes de Plantas/citologia , Raízes de Plantas/genética , Feixe Vascular de Plantas/citologia , Feixe Vascular de Plantas/genética , Feixe Vascular de Plantas/fisiologia , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Transdução de Sinais/fisiologia , Nicotiana/genética , Nicotiana/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação TranscricionalRESUMO
Infectious diseases are associated with low iron levels and the induction of hepcidin, the primary protein regulating cellular iron export. Bone morphogenetic protein 6 (BMP6), a key regulator of hepcidin expression, has not yet been analyzed in the plasma of patients with systemic inflammatory response syndrome (SIRS) or sepsis. An analysis of 38 SIRS, 39 sepsis, and 78 septic shock patients revealed similar levels of BMP6 in sepsis and septic shock, which were lower compared to patients with SIRS and healthy controls. Plasma BMP6 levels did not correlate with procalcitonin and C-reactive protein levels in patients with SIRS or sepsis/septic shock. Neither bacterial nor SARS-CoV-2 infections affected plasma BMP6 levels. There was no difference in BMP6 levels between ventilated and non-ventilated patients, or between patients with and without dialysis. Vasopressor therapy did not alter BMP6 levels. Survivors had plasma BMP6 levels similar to non-survivors. Due to the high variability of plasma BMP6 levels, these analyses have limited clinical relevance. Iron, ferritin, and transferrin levels were known in at least 50% of patients but did not correlate with plasma BMP6 levels. In conclusion, this study showed normal BMP6 plasma levels in SIRS, which are reduced in patients with sepsis and septic shock. This suggests that the commonly observed increase in hepcidin levels and the decline in iron levels in SIRS, sepsis, and septic shock are not due to higher BMP6.
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We share a case of a 54-year-old Caucasian immune-competent male with a suspected long latent visceral leishmaniasis presenting primarily with parasitic colitis, splenomegaly, and pancytopenia. Due to histopathologically and endoscopically mimicking ulcerative colitis the patient was initially treated for UC, until the parasites were identified and eradicated with liposomal Amphotericin B.
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BACKGROUND: Surfaces in close proximity to patients within hospitals may cause healthcare-associated infections. These surfaces are repositories for pathogens facilitating their transmission among staff and patients. Regular cleaning and disinfection of these surfaces provides only a temporary elimination of pathogens with inevitable recontamination. Antimicrobial coatings (AMC) of such surfaces may additionally reduce the risk of pathogen transmissions. The study aimed to find out whether photodynamic coatings can be effective even at very low light intensities. AIM: To evaluate the efficacy of a standard and a novel photodynamic AMC in a field study conducted in two ICUs at our university hospital. METHODS: The microbial burden was determined on three coatings: standard photodynamic AMC (A), a novel photodynamic AMC (B), and an inactive AMC as control (C). The control coating C was identical to standard coating A, but it contained no photosensitizer. During a 3-month period, 699 samples were collected from identical surfaces using eSwab and were analyzed (cfu/cm2). FINDINGS: Mean values of all surfaces covered with control coating (C) showed a microbial burden of 5.5 ± 14.8 cfu/cm2. Photodynamic AMC showed significantly lower mean value of 1.6 ± 4.6 CFU/cm2 (coating A; p<0.001) and 2.7 ± 9.6 (coating B; p<0.001). When considering a benchmark of 2.5 cfu/cm2, the relative risk for higher microbial counts was reduced by 52 % (coating A) or 40 % (coating B), respectively. CONCLUSIONS: Both photodynamic AMCs offer a substantial, permanent risk reduction of microbial counts on near patient surfaces in ICUs with low light intensities.
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SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9 regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC) were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival. The current study suggests that the imbalance between CE and FC levels is associated with disease severity and mortality in patients with COVID-19.
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Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections.
Assuntos
Biomarcadores , COVID-19 , Herpes Simples , Proteína S100A12 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/sangue , COVID-19/imunologia , Masculino , Feminino , Proteína S100A12/sangue , Pessoa de Meia-Idade , Biomarcadores/sangue , SARS-CoV-2/imunologia , Prognóstico , Idoso , Herpes Simples/diagnóstico , Herpes Simples/sangue , Adulto , Índice de Gravidade de Doença , Superinfecção/diagnóstico , Superinfecção/sangue , Farmacorresistência Bacteriana Múltipla , Neutrófilos/imunologia , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Enterococos Resistentes à VancomicinaRESUMO
BACKGROUND AND AIMS: During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection developed secondary sclerosing cholangitis (SSC) as a hepatobiliary complication. METHODS: 17 patients were endoscopically diagnosed and treated with COVID-19 SSC from February 2020 until October 2022 at our center. We retrospectively reviewed and analyzed the data to define risk factors, establish endoscopic treatment options, and to estimate incidence and outcomes. RESULTS: 258 patients with COVID-19 infection were admitted to our tertiary center and mechanically ventilated. 10 patients developed COVID-19 SSC in-house, and 7 patients were transferred for further endoscopic treatment. All 17 patients were mechanically ventilated, received vasoactive substances and 12 of them were treated with extracorporeal membrane oxygenation therapy. Endoscopic retrograde cholangiography (ERC) was performed in all patients to establish the diagnosis of COVID-19 SSC and evaluate endoscopic treatment options. All ERCs revealed biliary casts. 9 patients had developed severe rarefication of the intrahepatic bile ducts and 4 showed biliary strictures. As endoscopic treatment approaches, casts were removed repeatedly, and strictures were dilated. During the study period, 14 patients died (82%). 3 patients are in follow-up to reassess the need for liver transplantation. CONCLUSIONS: COVID-19 SSC was observed in 2.6 % of the patients with severe COVID-19 in our center. We show that endoscopic approaches offer the opportunity to extract casts and to treat biliary strictures. As the mortality rate of COVID-19 SSC is high, endoscopic treatment can be of great clinical relevance as a bridge to liver transplantation.